RET positive

This is the first reported case of selpercatinib-induced acalculous cholecystitis in a patient. The report highlighted the potential efficacy of selpercatinib in elderly patients while underscoring the risk of severe adverse events and emphasizing monitoring and personalized dose management.

In Japanese patients treated with selpercatinib, efficacy in whole patients was similar to the worldwide population, whereas AEs (especially liver dysfunction) was more severe than worldwide population. This result highlights the need for careful dose management strategies for Japanese patients.

This case highlights the potential of selpercatinib in the perioperative setting, suggesting that it induces tumor regression and enabling of curative surgery in early-stage RET fusion-positive NSCLC. Our findings support the further investigation of selpercatinib in early stages and provide a rationale for future treatment strategies of early-stage RET fusion-positive NSCLC patients.

The United States Food and Drug Administration (FDA) has approved pembrolizumab for MSI-high tumors or tumors with a high TMB. Larotrectinib and entrectinib have been approved for the treatment of NTRK gene fusion-positive tumors. Additionally, the combination of dabrafenib and trametinib has been approved for BRAF V600E mutations, and selpercatinib has been approved for RET fusion-positive cancers as of 2022. Positive responses to agnostic therapy, a significant milestone in cancer treatment, depend on the identification of new agnostic biomarkers. Ongoing research is focused on defining additional molecular changes, such as programmed death-ligand 1 (PD-L1), Kirsten rat sarcoma virus (KRAS), neuregulin 1 (NRG1), fibroblast growth factor receptor (FGFR), anaplastic lymphoma kinase (ALK), AKT serine/threonine kinase (AKT), human epidermal growth factor receptor 2 (HER2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and breast cancer gene (BRCA), as potential agnostic biomarkers in various cancer types.

Incorporating targeted therapy with surgery and tailored adjuvant treatment may lead to durable remission in selected patients with locally advanced disease. Prospective studies need to be conducted to further define the treatment sequencing and validate this multi-modal approach.

The combination of selpercatinib and cemiplimab was possible, with no new safety signals observed.

Our results show that the multitargeted SRC TKI dasatinib significantly enhanced the efficacy of RET TKIs in RET fusion-positive (RET+) NSCLC and PTC cells...Importantly, synergy was also observed with eCF506 (NXP900), a next-generation clinical SRC inhibitor. Finally, both SRC TKIs restored sensitivity in selpercatinib-resistant RET+ PTC cells. These results elucidate RET and SRC signaling crosstalk in RET+ NSCLC and PTC, suggesting that co-inhibiting SRC has clinical potential in TKI-naïve and -resistant RET+ cancers.

Adjuvant therapy with selpercatinib was continued postoperatively. The patient remained recurrence-free on continued follow-up with 17 months since diagnosis and 8 months since surgery.

P3, N=261, Active, not recruiting, Eli Lilly and Company | Trial completion date: Jun 2026 --> Jun 2030

Transbronchial needle aspiration confirmed lung adenocarcinoma, with RET fusion detected via gene panel testing. Treatment with selpercatinib resulted in a sustained partial response for over one year, providing the first clinical evidence supporting this targeted therapy in RET fusion-positive lung adenocarcinoma with miliary metastases.

2 weeks later, the corneal findings improved and visual acuity increased. The patient was much better 1 months later.DiscussionThis case report describes corneal edema with epithelial defect as a rare side effect of pralsetinib and highlights the importance of collaboration between oncologists and ophthalmologists.

After three cycles of pemetrexed plus cisplatin (PC) regimen combined with camrelizumab (a PD-1 inhibitor), a partial response (PR) was observed through chest computed tomography (CT) and brain magnetic resonance imaging (MRI). NSCLC patients who have PD-L1 overexpression and RET fusion-positivity may respond well to immunotherapy. Combining radiotherapy with immunotherapy may enhance local control of brain metastases.